Immunology lecture 12,13,14 Adaptive immunity
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- What three cell types constitute the adaptive immune response
- CD4 T cells, CD8 T cells, B cells
- What are Th1 cells characterized by
- production of gamma-interferon
- What are Th2 responses characterized by
- Production of interleukin 4
- What is the primary purpose of CD 8 cells
- killing host cells that have become infected with intracellular pathogens. They generally require help from CD4 T cells to achieve full activation
- What are B cells known for
- Producing antibodies. They generally require direct help from CD4 T cells to achieve full activation
- How is the adaptive immune system triggered
- Encounter with antigen
- What does the activation of T cells require
- Peptide + MHC; CD4 or CD8 coreceptor; costimulation (CD28) and cytokine signals (autocrine IL-2)
- What is the series of biochemical events in the process of T cell activation
- CD3 molecules become phosphorylated on ITAMs; tyrosine kinase Zap70 is recruited; stimulation of Calcium influx; activation of NF-kB, NFAT, and AP-1 (required for production of IL-2)
- How do the immunosuppressive drugs Cyclosporin A and FK506 function
- They inhibit the activity of calcineurin, blocking NFAT entry into the nucleus, IL-2 production, and T cell activation
- What are superantigens
- Toxins produced by certain pathogenic bacteria that bind to specific subsets of T cell receptors, causing polyclonal T cell activation
- What are mitogenic lectins
- Plant-derived carbohydrate products that bind to the T cell surface, causing clustering of cell surface receptors, mimicking antigen stimulation of the TCR, without the need for antigen presenting cells
- What happens when PMA and ionomycin are used together
- The T cell is fully activated, bypassing the need for TCR engagement by antigen and antigen presenting cells
- What initiates adaptive immunity
- T cell/dendritic cell interactions
- What role does the inflammatory response play in adaptive immunity
- It provides critical stimulation to the dendritic cell, resulting in dendritic cell maturation
- How are mature dendritic cells characterized
- By increased cell surface MHC and increased costimulatory molecules (B7)
- What are adjuvants
- The pathogen components that lead to augmentation of the adaptive immune response
- Besides dendritic cells, what other professional cells can present antigen to T cells
- Macrophages and B cells, but they are not nearly as important as dendritic cells for the activation of naive T cells
- What is special about effector T cells
- They are more sensitive to antigen and no longer require costimulation to become fully activated.
- What does interferon gamma do
- Activates macrophages, inducing killing activity
- What kind of immunity do Th1 cells stimulate
- cell-mediated immunity
- What results from loss of expression of L-selectin
- T cells no longer migrate to lymph nodes
- What happens from gain of expression of VLA-4
- T cells traffick to activated endothelia, at sites of peripheral inflammation
- What cytokines do Th2 cells release, and what do they do
-
IL-4 (stimulates B cell differentiation)
IL-5 (stimulates eosinophil production and maturation). Th2 primarily stimulates humoral immunity and cell-mediated immunity to parasitic worms - What is the primary cause of alleric reactions
- Th2 T cell responses
- Where are the two places Th2 effector T cells can go
- They can either remain in secondary lymphoid tissue, where they interact with B cells, inducing B cell differentiation, or they can migrate to peripheral tissues, where they secrete cytokines that can assist the innate immune response to parasitic worms
- What are the characteristics of memory CD4 T cells
- They are long lived; for a given antigen that has previously been encountered, there are approximately 100-fold more memory T cells than naive T cells of the same specificity; Memory T cells are more easily activated than naive T cells
- How do CD4 T cells help CD8 T cells
- They secret IL-2 and other cytokines in tissues where CD8 T cells are encountering antigen + MHC class 1, or by CD40L stimulation of dendritic cells
- Which cells express B7 ligand
- Professional APCs (Dentritic cells, macrophages, B cells). B7 binds to CD28
- What is the purpose of CD40L expression on CD4 cells
- This engages CD40 on the dendritic cell, causing the dendritic cell to express higher levels of B7
- What are three ways naive CD8 T cells are activated
-
1. Activated dendritic cells expressing MHC class 1, with costimulation from CD28
2. Dendritic cells plus help from CD4 T cells in the form of IL-2
3. Dendritic cells plus help from CD4 T cells expressing CD40L - What is special about CD8 effector T cells
- They no longer require costimulatory signals through CD28
- Killing via CD8 T cells is via what two mechanisms
-
1. Directed secretion of cytolytic granules towards the target cell. These granules cause perforation of the target cell's membrane
2. Expression of Fas ligand on the surface of the CD8 T cells, which engages Fas on the target cell, and triggers apoptosis - CD8 T cell killing is the predominant mechanism for elimination of what
- Viruses
- What is special about Listeria monocytogenes
- It is considered to be an intracellular bacteria, since phagocytosis by macrophages is insufficient to kill it
- What stimulates macrophage activation
- The combined action of IFN-gamma and CD40L
- What is the predominant mechanism of killing intracellular bacteria
- The production of reactive oxygen and NO by activated macrophages
- What is delayed type hypersensitivity (DTH)
- A Th-1 driven immune reaction that develops in the skin. It can create contact sensitivity seen with poison ivy or the tuberculin skin test. DTH lesions are characterized by induration (hard to the touch)
- What are T-reg cells
- Suppressor T cells that express the high affinity IL-2 receptor. They produce the inhibitory cytokines TGF-B and IL-10. They must directly contact target cells to mediate suppression
- What are the functions of T-reg cells
- Prevent autoimmunity; modulate immune responses to pathogens, preventing tissue damage; generate tolerance to self antigens at peripheral sites
- What does it mean for a B cell to be T dependent
- Most antigens encountered by B cells require CD4 T cell help in order to generate an antibody response to the antigen
- B cell activation is greatly enhanced by what complement
- C3d binding to the CD21/CD19/CD81 complement receptor complex
- Where is C3d deposited
- On pathogens that have been recognized by the complement system. It thus lets the B cell know that it has bound a foreign antigen
- What are the biochemical events that lead to B cell activation and antibody secretion
- Ig-alpha and Ig-Beta become phosphorylated on ITAMs; Syk (Zap70 relative) binds the ITAMs; activation of NF-kB, NFAT, AP-1
- What is the importance of NF-kB, NFAT, and AP-1 in B cells
- They are required for antibody secretion, secretion of autocrine cytokines, for B cell proliferation, and generation of memory B cells
- What will happen if a B cell is activated without CD4 T cell help
- It will only secrete IgM, and it will not undergo affinity maturation
- What is the result in the B cell of the CD40 signal in conjunction with cytokine signals from the CD4 T cell
- Immunoglobulin class switching and affinity maturation
- Help from CD4 T cells is crucial to the production and secretion of which antibodies
- IgG, IgA, IgE
- What do germinal centers contain
- Specialized antigen presenting cells called follicular dendritic cells (FDCs), which maintain clusters of opsonized antigen (iccosomes) on their cell surface for extended periods of time
- Where do plasma cells reside
- B cells follicles of lymph nodes and spleen and in the bone marrow
- What is special about non-protein antigens
- They cannot stimulate a CD4 T cell response. They are T-independent (TI)
- What is unique about TI carbohydrate and lipid antigens
- They have repetivite subunits, and are thus capable of very efficiently crosslinking the BCR and causing substantial BCR signaling
- What is a complication of spleenectomy
- Those who have lost the major reservoir of B cells are at particular risk for encapsulated bacteria, because their TI response is greatly reduced